This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Strategies for inducing life-long, protective immunity against HIV infection remain elusive. Herpesviruses establish persistent, life-long infection in humans and are divided into three different classes based on their genetics and biology. Epstein-Barr virus (EBV) is a gamma-1 herpesvirus that persists for life in an antigen presenting cell, ie B cell, and stimulates potent life-long anti-viral cellular and humoral immune responses. EBV-immortalized lymphoblastoid cell lines are commonly used in vitro for their immunostimulatory ability, EBV latent infection proteins can upregulate many cell genes associated with antigen presentation, and EBV carries fewer immune evasion genes compared to other herpesviruses. Thus, EBV biology is significantly different from other human herpesviruses, and EBV may provide unique advantages as a vaccine vector for inducing life-long immunity. All New and Old World non-human primates are naturally infected with herpesviruses closely related to EBV and in the same gamma-1, or lymphocryptovirus (LCV), genus. The LCV naturally infecting rhesus macaques (rhLCV) has been fully sequenced and has an identical repertoire of viral genes as EBV. We will use this EBV animal model to evaluate the ability of recombinant rhLCV expressing SIV or HIV antigens to induce humoral and cellular immune responses to the gamma-herpesvirus vaccines. These pilot studies will explore a novel approach for inducing life-long persistent vaccine responses and will also provide important new insights for EBV biology.